Chemical unfolding of human plasma vitronectin has demonstrated that the protein refolds at physiological strength to a multimeric form. Self-association of the protein following denaturation in 5M urea is prohibited by addition of 1.5M NaCl in the refolding medium. Differential scanning calorimetry was pursued in order to compare thermal denaturation of vitronectin under conditions of physiological and high ionic strength. The intrinsic heat capacity of the folded protein and the magnitude of the of the enthalpy of the denaturation were analyzed to provide information about the structural organization of the protein, since other methods indicate that the protein may be conformationally labile and loosely organized. Scanning calorimetry was performed at near neutral pH and at ph 4, to compare the heat capacities and enthalpies under the two sets of experimental conditions. Thermal denaturation was evaluated in the presence of saturating amounts of ligand, heparin, in order to determine whether the ligands binds preferentially to the native or denatured form of the protein.